Our Laboratory is interested in understanding how the nervous system regulates life span, and behavioral aspect of host pathogen interactions. We utilize a genetically tractable nematode, Caenorhabditis elegans as a model host. Neural regulation of innate immunity and avoidance of pathogenic microbes is an emerging and exciting area of research which has taken advantage of C. elegans genomics, genetics and neurobiology tools.We have found that the nervous system of C. elegans can regulate innate immune responses by induction of conserved signaling pathways such as p38 MAPK, unfolded protein response leading to production of antimicrobial peptides, lectin and mucin like molecules at the site of infection. We have also found that C. elegans avoids pathogenic Gram negative bacterium Pseudomonas aeruginosa and Gram positive bacterium Enterococcus faecalis using its sensory organs called amphid in the head and phasmid in the tail region.
Two major findings:
(a) Avoidance of P. aeruginosa requires odor sensory circuits of AWA and AWB neurons in C. elegans.
(b) Avoidance of E. faecalis requires chemosensory circuits of PHA neurons and neurotransmitters, serotonin and dopamine.
Current projects in the laboratory include :
i) Use of Genetically encoded calcium sensor (GECI) to investigate pathogen activated odorsensory circuits.
ii) Screen of P. aeruginosa mutant library to find volatile molecule that can activate C. elegans AWA odor sensory neurons.
iii) C. elegans PHA chemosensory neuron ablation and GECI strains to study worm responses to E. faecalis molecules.
iv) Is quorum sensing in E. faecalis required to induce avoidance response in C. elegans?
v) Nitric oxide induces resistance to stress in C. elegans via soluble guanylyl cyclases present in sensory neurons AQR, PQR and URX.
Methods used in our laboratory to study host pathogen Interactions and life span include C. elegans chemotaxis assays, learning and adaptation assays, creation of transgenic animals, measuring Calcium transients in worms with GECIs, gene knockdown by feeding RNAi, survival assays on pathogenic bacteria, life span assays, lipid staining, Nitric oxide treatment etc. We are also interested in microbial genetics which included screening and creation of mutant bacterial strains.
- Singh V & Aballay A. Endoplasmic reticulum stress pathway required for immune homeostasis is neurally controlled by arrestin-1. J Biol Chem 2012 287, 33191
- Sun J, Singh V, Kajino-Sakamoto R & Aballay A. (2011). Neuronal GPCR controls innate immunity by regulating non canonical unfolded protein response genes. Science332, 729
- Singh V & Aballay A. (2009). Regulation of DAF-16-mediated innate immunity in Caenorhabditis elegans. J Biol Chem284, 35580
- Styer KL, Singh V, Macosko E, Steele SE, Bargmann CI & Aballay A. (2008). Innate immunity in Caenorhabditis elegans is regulated by neurons expressing NPR-1/GPCR. Science 322, 460
- Singh V & Aballay A. (2006). Heat shock and genetic activation of HSF-1 enhance immunity to bacteria. Cell Cycle 5, 2443 (review)